Mitochondria:DiversityintheregulationofNLRP3inflammasomePrajwalGurung1,JohnR.Lukens1,2,andThirumala-DeviKanneganti11DepartmentofImmunology,St.JudeChildren’sResearchHospital,Memphis,TN,38105,USA2CenterforBrainImmunologyandGlia(BIG),DepartmentofNeuroscience,UniversityofVirginia,Charlottesville,VA,22908,USAAbstractRecentstudieshaveidentifiednewrolesformitochondriaintheregulationofautoinflammatoryprocesses.Emergingdatasuggeststhatthereleaseofdangersignalsfrommitochondriainresponsetostressandinfectionpromotestheformationoftheinflammatorysignalingplatformknownasinflammasomes.Activationofinflammasomesbydamagedmitochondriaresultsincaspase-1-dependentsecretionoftheinflammatorycytokinesIL-1βandIL-18,andaninflammatoryformofcelldeathreferredtoaspyroptosis.Here,wereviewrecentlydescribedmechanismsthathavebeenproposedtobeinvolvedinmitochondria-mediatedregulationofinflammasomeactivationandinflammation.Inaddition,wehighlighthowaberrantregulationofmitochondria-inducedinflammasomeactivationcentrallycontributestotheinflammatoryprocessthatareresponsibleforobesityandassociatedmetabolicdiseases.KeywordsMitochondria;NLRP3;inflammasome;metabolicdiseaseHistoricalperspectiveontheoriginandimportanceofmitochondriaIntheearly1960sitwasproposedthatthepresenceofmitochondriaincellsweretheresultofevolutionarysymbiosis,whichisoftenreferredtoasendosymbiosis[1].Severalstudieshavearguedthatmitochondriawereoriginallyseparatebacteriathatendedupinasymbioticrelationshipwithinmammaliancellsduringthecourseofevolution[2].Themitochondrionisamajororganellerequiredfornumerousfunctionswithinthecellandisessentialforsurvival.Oneoftheearliestfunctionsattributedtomitochondriaisinvolvementintheglycolysis/TCAcycle/electrontransportchain(seeGlossary)thatgeneratesenergyinthe©2014ElsevierLtd.Allrightsreserved.Correspondingauthor:Thirumala-DeviKanneganti(Thirumala-Devi.Kanneganti@StJude.org).ConflictofInterest:Theauthorsdeclarenocompetingfinancialinterests.Publisher'sDisclaimer:ThisisaPDFfileofanuneditedmanuscriptthath...
